Search Results (267)

Cystic fibrosis produces viscous mucus in the lung that increases bacterial invasion, causing persistent infections and subsequent inflammation. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most common infections in cystic fibrosis patients that are resistant to antibiotics. One antibiotic approved to treat these infections is levofloxacin (LVX), which functions to inhibit bacterial replication but can be further developed into tailorable particles. Nanoparticles are an emerging inhaled therapy due to enhanced targeting and delivery. The extracellular matrix (ECM) has been shown to possess pro-regenerative and non-toxic properties in vitro, making it a promising delivery agent. The combination of LVX and ECM formed into nanoparticles may overcome barriers to lung delivery to effectively treat cystic fibrosis bacterial infections. Our goal is to advance CF care by providing a combined treatment option that has the potential to address both bacterial infections and lung damage. Two hybrid formulations of a 10:1 and 1:1 ratio of LVX to ECM have shown neutral surface charges and an average size of ~525 nm and ~300 nm, respectively. The neutral charge and size of the particles may suggest their ability to attract toward and penetrate through the mucus barrier in order to target the bacteria. The NPs have also been shown to slow the drug dissolution, are non-toxic to human airway epithelial cells, and are effective in inhibiting Pseudomonas aeruginosa and Staphylococcus aureus. LVX-ECM NPs may be an effective treatment for pulmonary CF bacterial treatments. Full article

Background: The introduction of cystic fibrosis transmembrane conductance regulator modulators, especially the triple therapy elexacaftor, tezacaftor, ivacaftor (ETI), has improved outcomes in people with cystic fibrosis (pwCF), reducing underweight but increasing overweight rates. Objectives: This study investigates the effect of ETI on appetite control, body composition, and energy balance during a 3-week inpatient rehabilitation programme with regular exercise. Methods: In 54 pwCF (38 on ETI, 16 without ETI), changes in body composition (fat mass index, FMI; fat-free mass index, FFMI) and energy balance (calculated from body composition changes) were assessed. Appetite control was evaluated via plasma peptide YY (PYY) levels and post-exercise meal energy intake. Results: The programme significantly increased BMI (+0.3 ± 0.1 kg/m²; CI 0.1–0.4) and energy balance (+4317 ± 1976 kcal/3 weeks), primarily through FFMI gains (+0.3 ± 0.1 kg/m²; CI 0.1–0.4). Despite higher post-exercise meal energy intake and a tendency towards lower PYY levels in the ETI group, changes in body composition and energy balance did not differ between groups. This is explained by a higher prevalence of exocrine pancreatic insufficiency in the ETI group (92% vs. 50%, p < 0.001). Small sample sizes limit the interpretation of data on appetite control and energy intake. Conclusions: A 3-week inpatient rehabilitation programme improved body composition in pwCF, without resulting in a more positive energy balance with ETI therapy. This is due to a higher prevalence of pancreatic insufficiency in this group. Full article

Allergy is recognized as a public health problem with pandemic consequences and is estimated to affect more than 50% of Europeans in 2025. Prebiotic and probiotic food implementation has recently emerged as an alternative strategy to promote immunomodulatory beneficial effects in allergic patients. Among prebiotics, Phaeophyceae algae represent a niche of research with enormous possibilities. The present study aims to evaluate the in vitro prebiotic potential of fucoidan from Fucus vesiculosus, Macrocystis pyrifera, and Undaria pinnatifida algae, to promote the growth of Limosilactobacillus reuteri and Lacticaseibacillus rhamnosus GG as probiotic bacteria added to the formulation of a novel yogurt. Concentrations of fucoidan of 100 and 2000 µg/mL were added to reference growth media and kinetic growth curves for both microorganisms were fitted to the Gompertz equation. Optimized prebiotic conditions for fucoidan were selected to validate in vitro results by means of the formulation of a novel fermented prebiotic yogurt. Conventional yogurts (including Streptococcus thermophilus and Lactobacillus delbrueckii subs. bulgaricus) were formulated with the different fucoidans, and production batches were prepared for L. rhamnosus and L. reuteri. Increased L. reuteri and L. rhamnosus populations in 1.7–2.2 log₁₀ cycles just after 48 h of in vitro exposure were detected in fucoidan supplemented yogurt. M. pyrifera and U. pinnatifida fucoidans were the most effective ones (500 µg/mL) promoting probiotic growth in new formulated yogurts (during the complete shelf life of products, 28 days). Diet supplementation with fucoidan can be proposed as a strategy to modulate beneficial microbiota against allergy. Full article

Background: Staphylococcus aureus is a significant pathogen causing both local and systemic infections in children, with deep tissue involvement leading to severe complications. This study aimed to assess clinical manifestations and identify risk factors for deep tissue involvement in pediatric S. aureus infections. Methods: All children between 1 month and 18 years who had S. aureus growth in blood, pus, or joint fluid culture were included. Results: A total of 61 patients (median age 55 months) were included, with 22.9% having deep tissue infections. Osteoarticular infections, pyomyositis, and pulmonary involvement were common. Deep-seated infections were significantly associated with community-acquired infections and positive hemocultures after 72 h (p < 0.01). Laboratory results showed significantly higher levels of C-reactive protein, sedimentation rate, D-dimer, and fibrinogen in the group with deep-seated infections (p = 0.02, p = 0.018, p = 0.01, and p = 0.015, respectively). The decision tree model showed that the first indicator of deep-seated infection was a D-dimer level above 1.15 mg/L, followed by a fibrinogen level above 334 mg/dL. Conclusions: Deep-seated S. aureus infections are more frequently associated with community-acquired cases, persistent hemoculture positivity, and methicillin-susceptible Staphylococcus aureus (MSSA) strains. Additionally, elevated D-dimer and fibrinogen levels may serve as valuable markers for identifying deep-seated infections in pediatric patients. Full article

Background and Objectives: Pediatric pulmonary medicine relies heavily on accurate lung function assessment, yet conventional spirometry presents challenges in children due to cooperation requirements. In this context, the interrupter resistance technique (Rint), a method used in pediatric pulmonology, offers a potentially more feasible alternative for evaluating airway resistance in younger populations. This study aimed to assess the feasibility and clinical concordance between expiratory interrupter resistance (Rint(e)) and standard spirometry in healthy children under 8 years, thus contributing to the development of age-appropriate pulmonary function testing in pediatric medicine. Materials and Methods: A cross-sectional study was conducted on 200 healthy children (aged 2–8 years) in Tunisia. Pulmonary measurements were taken using a handheld device for both Rint(e) and spirometry. Feasibility rates were calculated, and correlations between the techniques were statistically analyzed. Results: Rint(e) showed significantly higher feasibility than spirometry (82.5% vs. 34.5%, p < 0.05). While older children had higher success rates with both techniques, feasibility was independent of sex, BMI, and passive smoking exposure. Moderate negative correlations were found between log Rint(e) and FEV1/FVC indices. Conclusions: In pediatric pulmonary assessment, Rint(e) demonstrated higher feasibility than spirometry among young children, making it a practical complementary method in clinical settings. However, due to only moderate correlation with spirometric indices, Rint(e) cannot yet replace spirometry in diagnostic use. Its integration into pediatric medicine may help address the gap in functional respiratory evaluation for children under the age of 8. Full article

Objective: The objective of this study was to analyze respiratory muscle function in children and adolescents with cystic fibrosis (CF) treated with Elexacaftor/Tezacaftor/Ivacaftor (ETI) compared to healthy individuals, based on the hypothesis that CFTR modulators may improve respiratory muscle strength. Methods: A descriptive, observational, cross-sectional study was conducted with patients with CF treated with ETI aged 6–18 years. Lung function, maximal expiratory and inspiratory pressures (MIP and MEP), diet quality (KIDMED), and physical activity levels (PAQ) were assessed. The student’s t-test or the Mann–Whitney U-test was used to compare differences between groups. The effect size was calculated with Cohen’s d. Significance level was set as a p-value < 0.05. Results: A total of 48 children and adolescents (60.4% male) were analyzed in this study (24 healthy and 24 with CF). The participants with CF had mild pulmonary involvement. No significant differences were found in respiratory muscle strength between groups (MEP_max p = 0.440, MIP_max p = 0.206). Patients with CF showed lower KIDMED (p = 0.022) and PAQ (p = 0.010) scores. However, the MIP and MEP values observed in CF participants were higher than those reported in previous studies conducted before the introduction of ETI modulators. Conclusions: Children and adolescents with CF treated with ETI showed respiratory muscle strength comparable to that of healthy controls. Despite differences in lifestyle factors, these findings may reflect a positive impact of CFTR modulators on respiratory muscle function, although further longitudinal and controlled studies are needed. Full article

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder marked by neurological regression, autonomic dysfunction, seizures, and significant sleep and breathing abnormalities. About 80% of affected individuals, especially young children, experience sleep disturbances such as insomnia, sleep-disordered breathing, nocturnal vocalizations, bruxism, and seizures. Breathing irregularities during sleep—like apnea, alternating hyperventilation, and hypoventilation—are common, with both obstructive and central sleep apnea identified through polysomnography. This review focuses on the prevalent sleep disorders in children with Rett syndrome and highlights current recommendations for the management of sleep disorders. Full article

Background: Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by recurrent sinopulmonary infections due to motile cilia defects. The disease is genetically heterogeneous, with abnormalities in structural ciliary proteins. Zinc finger MYND-type containing 10 (ZMYND10) is essential for the assembly of outer dynein arms (ODA), with chaperones like Glucose-regulated protein 78 (GRP78) facilitating protein folding. This study investigates ZMYND10 and Dynein axonemal heavy chain 5 (DNAH5) mutations in individuals with PCD. Methods: Eight individuals aged 14–22 with clinical PCD symptoms and confirmed DNAH5 mutations were included. We analyzed the correlation between DNAH5 abnormalities and preassembly/chaperone proteins using immunofluorescence labeling. Nasal swabs were double-labeled (DNAH5–β-tubulin, β-tubulin–ZMYND10, β-tubulin–GRP78) and examined via fluorescence microscopy. Serum metabolomics and proteomics were also assessed. Results: The corrected total cell fluorescence (CTCF) levels of DNAH5, ZMYND10, and GRP78 were significantly different between PCD individuals and controls. Metabolomic analysis showed reduced valine, leucine, and isoleucine biosynthesis, with increased malate and triacylglycerol biosynthesis, malate-aspartate and glycerol phosphate shuttles, and arginine/proline metabolism, suggesting mitochondrial and ER stress. Conclusions: The altered expression of DNAH5, ZMYND10, and GRP78, along with metabolic shifts, points to a complex link between ciliary dysfunction and cellular stress in PCD. Further studies are needed to clarify the underlying mechanisms. Full article

Poor sleep quality and excessive daytime sleepiness are commonly reported by individuals with cystic fibrosis. The potential impact of comorbid sleep-disordered breathing (SDB), particularly obstructive sleep apnea (OSA), has not been extensively studied in the CF population. At present, there are no specific recommendations available to help clinicians identify patients with CF who are at increased risk of sleep disorders. Home sleep apnea testing using a validated peripheral arterial tonometry (PAT) device may offer an accurate diagnosis of OSA in a more convenient and low-cost method than in-lab polysomnography. In this single-center study of 19 adults with CF, we found an increased prevalence of OSA among individuals with CF compared to general population estimates. Although associations with an FEV < 70% predicted and a modified Mallampati score ≥ 3 were observed, these odds ratios did not reach statistical significance, likely reflecting limited power in this small pilot sample. There was no association found between the self-reported presence of nocturnal cough or snoring and OSA. We also found no association between OSA and abnormal scores on commonly used, validated sleep questionnaires, suggesting that CF-specific scales may be needed for effective screening in the CF clinic. Full article

Introduction: Gentrification, commonly defined as low-socioeconomic-status (SES) neighborhoods experiencing rapid increases in rental value, can lead to changes in the built and social neighborhood environment. Schools are an important location for pollutant exposure and child opportunities because children spend significant time in school. Given their central role in both environmental and social contexts, we examined the relationship between gentrification, pollutants, and child opportunity near schools in New York City. Methods: School locations (N_total = 1482) were classified into gentrifying (n = 624), non-gentrifying (n = 198), and higher-SES (ineligible for gentrification; n = 660) neighborhoods. Annual average pollutant levels (black carbon (BC), fine particulates (PM_2.5), nitrogen dioxide (NO₂)) were assessed near schools. Child opportunity index (COI 2.0) was used to evaluate overall opportunity and three domains: education; health/environment; social/economic. Results: On average, pollution was highest in gentrifying neighborhoods compared to non-gentrifying (5–8.6% difference) and higher-SES (4.8–14.8% difference) neighborhoods. Average air pollution levels remained consistently higher in gentrifying neighborhoods both before and after gentrification compared to non-gentrifying and higher-SES neighborhoods. Regarding childhood opportunity, education, and social/economic opportunities were better and health/environment opportunities were worse in gentrifying compared to non-gentrifying neighborhoods. Conclusions: Gentrifying neighborhoods are at risk for higher exposure to pollutants and lower health/environment childhood opportunities compared to other neighborhoods. Full article

Background/Objectives: Pediatric obstructive sleep apnea (OSA) is a prevalent medical condition, affecting 1–5% of non-syndromic children and 30–90% of children with Down syndrome. Given the severity of the condition and the associated health risks, early and effective treatment is crucial. However, current treatment modalities are often invasive or suffer from poor patient adherence. Additionally, adenotonsillectomy, the first-line treatment in pediatric OSA, seems not to be effective in every child, leaving children with residual OSA postoperatively. These challenges are particularly pronounced in high-risk populations, such as children with Down syndrome, highlighting the need for alternative therapeutic strategies. Therefore, a protocol is presented to evaluate the effectiveness of orofacial myofunctional therapy (OMT) as a treatment for OSA in two pediatric populations: (1) Non-syndromic children aged 4–18 years: 10 weeks of OMT. (2) Children with Down syndrome aged 4–18 years: 20 weeks of OMT. Effects of the OMT program will be evaluated on: sleep parameters (e.g., obstructive Apnea–Hyponea Index (oAHI), snoring frequency); orofacial functions (e.g., breathing pattern, tongue position at rest); quality of life outcomes. Methods: A pretest–posttest design will be used to evaluate the effectiveness of OMT in both children with and without Down syndrome and OSA. Both objective measures and patient-reported outcomes are being collected. Results: OMT is expected to improve orofacial functions, reduce OSA severity and symptoms, and enhance quality of life in both non-syndromic and syndromic children. Conclusions: This multidisciplinary research protocol, involving collaboration between ENT specialists and speech-language pathologists, aims to provide a comprehensive understanding of the potential benefits of OMT in treating OSA. Full article

Cystic Fibrosis (CF) is a common genetic disease in the United States, resulting from mutations in the Cystic Fibrosis transmembrane conductance regulator (cftr) gene. CFTR modulators, particularly Elexacaftor/Tezacaftor/Ivacaftor (ETI), have significantly improved clinical outcomes for patients with CF. However, many CFTR mutations are not eligible for CFTR modulator therapy due to their rarity. In this study, we report that a patient carrying rare complex CFTR mutations, c.1680-877G>T and c.3067_3072delATAGTG, showed positive clinical outcomes after ETI treatment. We demonstrate that ETI was able to increase the expression of CFTR harboring c.3067_3072delATAGTG in a heterologous system. Importantly, patient-derived nasal epithelial cells in an air–liquid interface (ALI) culture showed improved CFTR function following ETI treatment. These findings supported the initiation of ETI with the patient. Retrospective studies have suggested that the patient has shown small but steady improvement over the past two years in several clinical metrics, including lung function, body mass index (BMI), and sweat chloride levels. Our studies suggest that ETI could be beneficial for patients carrying c.3067_3072delATAGTG. Full article

Background: The symptoms of cow’s milk allergy (CMA) can vary widely in severity and course, so diagnosis and treatment are still challenging. Objective: This study aims to establish the phenotype of severe CMA in children with the greatest improvement following the application of amino acid-based formula (AAF). Methods: This is a post hoc analysis of data from the multicenter, real-life study assessing the clinical effectiveness of a 5-week AAF intervention in 232 infants with severe CMA. A cluster analysis based on symptom severity at the 1st visit was performed. The differences in the severity scale of each symptom before and after the intervention were assessed and compared within and between clusters. The clustering results were validated in a separate cohort of infants with CMA (n = 157). Results: Three clusters were identified: cluster A (38.8% of patients) with moderate-to-severe gastrointestinal symptoms, cluster B (34.1%) with severe skin symptoms, and cluster C (25.9%) with combined moderate-to-severe gastrointestinal and severe skin symptoms. In the validation cohort, three clusters with the same pattern of symptoms were observed among children with moderate-to-severe CMA. The multivariate model of linear regression showed that severity score reductions after AAF treatment were significantly higher in cluster C than in clusters A and B, in children with a positive family history of allergy, and in children with growth retardation at baseline. Conclusion: Symptoms of severe CMA in children are grouped into three distinct phenotypes—gastrointestinal, skin, and combined gastrointestinal and skin. The most significant improvement after AAF implementation was obtained in patients with a combined phenotype. Full article

Theoretical background: The study of psychological well-being in children and adolescents living with chronic illness is of particular relevance, as the physical and psychosocial aspects of the illness can have a significant impact on their quality of life. Previous research has highlighted that depression, nonproductive thoughts and various aspects of problematic internet use may be related to life satisfaction and ways of coping with illness. This study aims to examine how depression, nonproductive thoughts, and problematic internet use interact with illness perception and burden to affect psychological well-being and life satisfaction. Methods: A cross-sectional study was conducted with 207 chronically ill children aged 10–18 years. The children, aged between 10 and 18 years old, attended regular check-ups in different specialities (gastroenterology, pulmonology, onco-haematology, and paediatric rehabilitation). A cross-sectional study was carried out using psychological instruments to measure life satisfaction (SWLS), nonproductive thoughts (NPG-K), problematic internet use (PIU-Q), illness perception (PRISM) and illness burden (PRISM-D, IIRS), and depression (BDI-R). Spearman rank correlation analysis was used to explore the associations between variables. Results: Life satisfaction was negatively related to nonproductive thoughts (r = −0.28, p < 0.001), internet obsession (r = −0.20, p < 0.01), and internet neglect (r = −0.20, p = 0.004). Conversely, a positive correlation was found with the PRISM (r = 0.14, p = 0.042), suggesting that less dominance of illness detection is associated with higher life satisfaction. Depression and nonproductive thoughts showed a strong positive relationship (r = 0.49, p < 0.001), and depression and problematic internet use also showed significant correlations for the obsession, neglect and control subscales (r = 0.23–0.29, all p < 0.001). Cluster analysis identified three psychological profiles: ‘positive fighters’, ‘avoidant sufferers’, and ‘negative observers’, distinguished by differences in depression, nonproductive thoughts, illness burden, and well-being. Conclusions: The results suggest that the quality of life of children and adolescents with chronic illness is significantly affected by mental health factors, particularly depression, nonproductive thoughts and problematic internet use. Illness perception and illness-related distress also play a key role in shaping life satisfaction and overall psychosocial well-being. These findings underscore the need for targeted psychological interventions in pediatric chronic care to enhance well-being and promote adaptive coping and suggest that psychological interventions and targeted psychosocial support can significantly improve these children’s quality of life. Further research is needed to explore intervention options and to develop optimal support strategies. Full article

Accurate genetic diagnosis is essential for appropriate treatment in cystic fibrosis (CF). Large copy number variants like duplications in the CFTR gene are rare and often classified as variants of uncertain significance (VUSs) due to unknown characteristics of the inserted material, complicating diagnosis and treatment decisions. We identified a previously uncharacterized exon 22 duplication (CFTRdup22) in the CFTR gene in two anamnestically unrelated people with CF, both exhibiting a mild phenotype. Initial classification as a VUS was based on standard genetic testing. We employed a custom next-generation sequencing (NGS) panel to determine the exact breakpoints of the duplication and conducted mRNA sequencing to confirm its effect on splicing. DNA and RNA analyses allowed for precise breakpoint determination, confirming that the duplication was in tandem and the reading frame remained intact. This, as well as a residual CFTRdup22 function of ~30% as measured via intestinal current measurement, is consistent with a clinically milder CF phenotype. Collectively, the precise characterization of the variants’ breakpoints, localization and orientation enabled us to reclassify the variant as likely pathogenic. This study highlights the importance of advanced genetic techniques, such as NGS and breakpoint analysis, in accurately identifying CF-causing variants. It underscores the importance of a comprehensive approach and persistence when suspecting a specific genetic condition. This can aid in reclassifying VUSs, providing a definitive diagnosis for the affected family and enabling appropriate therapeutic interventions, including the use of CFTR modulators. Full article